P354: REAL-WORLD ANALYSIS OF THE RISKS OF THROMBOTIC AND BLEEDING EVENTS IN PATIENTS RECEIVING PEGYLATED ASPARAGINASE FOR TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: B. Mautner, B. Brewer, J. Mort, E. Pierce, F. Ghamsari, S. Dibenedetto, E. Morse, L. Wells, A. Morris, C. Allen, I. Patel, D. D’Souza, C. Jackson, M. Perciavalle, B. Yelvington, R. Miller, K. Abernathy, K. Walsh, H. Wolfe, S. Locke, D. Reed, V. Duong, B. Dholaria, T. LeBlanc, R. Shallis, M. Keng, B. Horton, F. El Chaer
Journal: HemaSphere (2022)

Background: The prognosis of younger adult patients with acute lymphoblastic leukemia (ALL) has improved with the adoption of pediatric-inspired chemotherapy regimens. PEGylated asparaginase (PEG-Asp) is essential to these regimens but is associated with an increased risk of coagulopathy, venous thromboembolism, and depletion of antithrombin III (AT3). There are limited data evaluating the risk of clinical coagulopathy (thrombosis and bleeding) and the optimal antithrombotic interventions in these patients are unknown. Aims: We aimed to assess the risk of thrombotic and bleeding events in patients with ALL treated with PEG-Asp and compare the treatment modalities with either AT3 + fibrinogen repletion vs the addition of prophylactic anticoagulation (AC) with either subcutaneous heparin 5000 TID or subcutaneous lovenox 30-40mg/day. Methods: We performed a multicenter retrospective analysis of patients ≥ 18 yo who received PEG-Asp for B- or T-ALL as part of multiagent chemotherapy from 2015-2020 treated across 6 US academic institutions. Categorical variables were summarized using means and standard deviations. The former was compared using Fisher’s exact test; the latter was compared using either the Wilcoxon text (for two groups) or the Kruskal-Wallis (for more than two groups) as appropriate. One way ANOVA test was used to compare continuous variables. Results: Our study included 129 treated patients who met eligibility criteria for induction and 73 patients who underwent post-induction therapy. During induction, the majority of the patients (90%) had AT3 and fibrinogen repletion, while only 10% received additional prophylactic anticoagulation. The rates of any thrombotic events were lower in the AT3/cryoprecipitate-only treatment group (18% vs 50%, p=0.015). Venous thromboembolism accounted for the majority of the thrombotic events (91% and 100% in the AT3/cryoprecipitate vs AT3/cryoprecipitate + prophylactic anticoagulation, respectively). Bleeding rates were numerically higher in patients who received AT3/cryoprecipitate + prophylactic anticoagulation (33% vs 14%, p=0.18). The rates of thromboses or bleeding events were not different when either prednisone or dexamethasone were included in the induction treatment regimen. During the post-induction phase, the rates of thrombotic and bleeding events were similar across all groups. The median time to thrombotic event was 11 days after the last PEG-Asp administration during induction, and 123 days during post-induction. Image:Summary/Conclusion: Although the increased thrombotic risk in adult patients receiving PEG-Asp is well-characterized, rates of reported thromboses vary widely. Studies examining bleeding risk associated with PEG-Asp regimens are even scarcer and with more variable outcomes. In our study, there was both a statistically significant increase in the rate of any thrombotic event as well as a trend towards increased bleeding in patients receiving AT3/cryoprecipitate + prophylactic anticoagulation versus those receiving AT3/cryoprecipitate alone. More investigation into the relative thrombotic and bleeding risks associated with PEG-Asp is needed to determine optimal antithrombotic interventions in adult patients with ALL.